title: Mechanical properties of interphase nuclei probed by cellular strain application.
abstract: The mechanical properties of the interphase nucleus have important implications for cellular function and can reflect changes in nuclear envelope structure and/or chromatin organization. Mutations in the nuclear envelope proteins lamin A and C cause several human diseases, such as Emery-Dreifuss muscular dystrophy, and dramatic changes in nuclear stiffness have been reported in cells from lamin A/C-deficient mice. We have developed a cellular strain technique to measure nuclear stiffness in intact, adherent cells and have applied this experimental method to fibroblasts from mouse models of Emery-Dreifuss muscular dystrophy and to skin fibroblasts from laminopathy patients and healthy control subjects. The experimental protocol is based on measuring induced nuclear deformations in cells plated on a flexible silicone substrate; the nuclear stiffness can subsequently be inferred from the ratio of induced nuclear strain to the applied membrane strain. These experiments reveal that lamins A and C are important determinants of nuclear stiffness and that lamin mutations associated with muscular dystrophies and other laminopathies often result in disturbed nuclear stiffness that could contribute to the tissue-specific disease phenotypes.
authors.affiliation: Department of Medicine, Cardiovascular Division, Brigham and Women's Hospital/Harvard Medical School, Cambridge, MA, USA.
authors.forename: Jan
authors.initials: J
authors.lastname: Lammerding
authors.forename: Richard T
authors.initials: RT
authors.lastname: Lee
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D002467:Cell Nucleus / Q000378:metabolism* / Q000502:physiology*; D006801:Humans; D034904:Lamin Type A / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009136:Muscular Dystrophies / Q000378:metabolism
chemical_list: D034904:Lamin Type A; C440308:lamin C